Despite the advent of new and aggressive
therapeutics,
breast cancer remains a leading killer among women; hence there is a need for the prevention of this disease. Several naturally occurring
polyphenols have received much attention for their health benefits, including anti-carcinogenic properties. Two of these are
resveratrol, a component of red grapes, and
epigallocatechin-3-gallate (EGCG), the major
catechin found in
green tea. In this study, we tested the hypothesis that these two
polyphenols protect against chemically-induced
mammary cancer by modulating mammary gland architecture, cell proliferation, and apoptosis. Female Sprague-Dawley CD rats were exposed to either
resveratrol (1 g/kg AIN-76A diet), EGCG (0.065% in the
drinking water), or control diet (AIN-76A) for the entirety of their life starting at birth. At 50 days postpartum, rats were treated with 60 mg dimethylbenz[a]
anthracene (DMBA)/kg
body weight to induce
mammary cancer.
Resveratrol, but not EGCG, suppressed mammary
carcinogenesis (fewer
tumors per rat and longer
tumor latency). Analysis of mammary whole mounts from 50-day-old rats revealed that
resveratrol, but not EGCG, treatment resulted in more differentiated lobular structures.
Bromodeoxyuridine (
BrdU) incorporation studies showed that
resveratrol treatment caused a significant reduction in proliferative cells in mammary terminal ductal structures at 50 days postpartum, making them less susceptible to
carcinogen insult. The epithelial cells of terminal end buds in the mammary glands of
resveratrol-treated rats also showed an increase in apoptotic cells compared to the control or EGCG-treated rats as measured by
a DNA fragmentation assay. At the given doses,
resveratrol treatment resulted in a serum
resveratrol concentration of 2.00 microM, while treatment with EGCG resulted in a serum EGCG concentration of 31.06 nM. 17beta-Estradiol,
progesterone, and
prolactin concentrations in the serum were not significantly affected by
resveratrol or EGCG. Neither
polyphenol treatment resulted in toxicity as tested by alterations in
body weights, diet and drink consumptions, and day to vaginal opening. We conclude that
resveratrol in the diet can reduce susceptibility to
mammary cancer, while EGCG in the
drinking water at the dose used was not effective.